Clinimetrics in rehabilitation medicine: current issues in developing and applying measurement instruments 1

Clinimetrics in rehabilitation medicine, i.e. the field of developing, evaluating and applying measurement instruments, has undergone considerable progress. Despite this progress, however, several issues remain. These include: (i) selection of an instrument out of the wide range available; (ii) using an instrument in a variety of diagnostic groups; (iii) using an instrument in individual patients, as opposed to a group of patients; and (iv) the use of instruments in clinical practice. This paper reviews these issues, as well as current attempts at resolving them. Illustrative examples are given. It is concluded that solutions seem to be available, but considerable research effort is required to make these a reality. Clinimetrics in rehabilitation medicine remains a field with challenging opportunities for researc

Diabetes, Glycemic Control, and New-Onset Heart Failure in Patients With Stable Coronary Artery Disease: Data from the Heart and Soul Study

OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and A1C with incident heart failure in outpatients with stable CAD and no history of heart failure (average follow-up 4.1 years). RESULTS Of 839 participants, 200 had diabetes (23.8%). Compared with patients who did not have diabetes, those with diabetes had an increased risk of heart failure (hazard ratio [HR] 2.17 [95% CI 1.37-3.44]). Adjustment for risk factors for CAD (age, sex, race, smoking, physical inactivity, obesity, blood pressure, and LDL cholesterol), interim myocardial infarction, and myocardial ischemia did not alter the strength of the association between diabetes and heart failure. After inclusion also of other risk factors for heart failure (left ventricular ejection fraction, diastolic dysfunction, and C-reactive protein) and medication use, diabetes remained an independent predictor of heart failure (HR 3.34 [95% CI 1.65-6.76]; P = 0.001). Each 1% increase in A1C concentration was associated with a 36% increased HR of heart failure hospitalization (HR 1.36 [95% CI 1.17-1.58]). CONCLUSIONS In patients with stable CAD who are free from heart failure at baseline, diabetes and glycemic control are independent risk factors for new-onset heart failure. The mechanisms by which diabetes and hyperglycemia lead to heart failure deserve further study, as the association is independent of baseline functional assessment of ischemia, systolic and diastolic function, and interim myocardial infarction

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Evasion of influenza A viruses from innate and adaptive immune responses

The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the current knowledge about immune evasion can be used to improve influenza A vaccination strategies

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Interexaminer Agreement and Reliability of an Internationally Endorsed Screening Framework for Cervical Vascular Risks Following Manual Therapy and Exercise:The Go4Safe Project

Objective: Clinicians are recommended to use the clinical reasoning framework developed by the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) to provide guidance regarding assessment of the cervical spine and potential for cervical artery dysfunction prior to manual therapy and exercise. However, the interexaminer agreement and reliability of this framework is unknown. This study aimed to estimate the interexaminer agreement and reliability of the IFOMPT framework among physical therapists in primary care. Methods: Ninety-six patients who consulted a physical therapist for neck pain or headache were included in the study. Each patient was tested independently by 2 physical therapists, from a group of 17 physical therapists (10 pairs) across The Netherlands. Patients and examiners were blinded to the test results. The overall interexaminer agreement, specific agreement per risk category (high-, intermediate-, and low-risk), and interexaminer reliability (weighted κ) were calculated. Results: Overall agreement was 71% (specific agreement in high-risk category = 63%; specific agreement in intermediate-risk category = 38%; specific agreement in low-risk category = 84%). Overall reliability was moderate (weighted κ = 0.39; 95% CI = 0.21-0.57) and varied considerably between pairs of physical therapists (κ = 0.14-1.00). Conclusion: The IFOMPT framework showed an insufficient interexaminer agreement and fair interexaminer reliability among physical therapists when screening the increased risks for vascular complications following manual therapy and exercise prior to treatment. Impact: The IFOMPT framework contributes to the safety of manual therapy and exercise. It is widely adopted in clinical practice and educational programs, but the measurement properties are unknown. This project describes the agreement and reliability of the IFOMPT framework

Posttreatment Ischemic Lesion Evolution Is Associated With Reduced Favorable Functional Outcome in Patients With Stroke

BACKGROUND AND PURPOSE: Ischemic lesion volume can increase even 24 hours after onset of an acute ischemic stroke. In this study, we investigated the association of lesion evolution with functional outcome and the influence of successful recanalization on this association. METHODS: We included patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) who received good quality noncontrast CT images 24 hours and 1 week after stroke onset. The ischemic lesion delineations included infarct, edema, and hemorrhagic transformation. Lesion evolution was defined as the difference between the volumes measured on the 1-week and 24-hour noncontrast CTs. The association of lesion evolution with functional outcome was evaluated using unadjusted and adjusted logistic regression. Adjustments were made for baseline, clinical, and imaging parameters that were associated P<0.10) in univariate analysis with favorable functional outcome, defined as modified Rankin Scale score of ≤2. Interaction analysis was performed to evaluate the influence of successful recanalization, defined as modified Arterial Occlusion Lesion score of 3 points, on this association. RESULTS: Of the 226 patients who were included, 69 (31%) patients achieved the favorable functional outcome. Median lesion evolution was 22 (interquartile range, 10–45) mL. Lesion evolution was significantly inversely correlated with favourable functional outcome: unadjusted odds ratio, 0.76 (95% CI, 0.66–0.86; per 10 mL of lesion evolution; P<0.01) and adjusted odds ratio: 0.85 (95% CI, 0.72–0.97; per 10 mL of lesion evolution; P=0.03). There was no significant interaction of successful recanalization on the association of lesion evolution and favorable functional outcome (odds ratio, 1.01 [95% CI, 0.77–1.36]; P=0.94). CONCLUSIONS: In our population, subacute ischemic lesion evolution is associated with unfavorable functional outcome. This study suggests that even 24 hours after onset of stroke, deterioration of the brain continues, which has a negative effect on functional outcome. This finding may warrant additional treatment in the subacute phase

Risk factors of late lesion growth after acute ischemic stroke treatment

BackgroundEven days after treatment of acute ischemic stroke due to a large vessel occlusion, the infarct lesion continues to grow. This late, subacute growth is associated with unfavorable functional outcome. In this study, we aim to identify patient characteristics that are risk factors of late, subacute lesion growth. MethodsPatients from the MR CLEAN trial cohort with good quality 24 h and 1-week follow up non-contrast CT scans were included. Late Lesion growth was defined as the difference between the ischemic lesion volume assessed after 1-week and 24-h. To identify risk factors, patient characteristics associated with lesion growth (categorized in quartiles) in univariable ordinal analysis (p < 0.1) were included in a multivariable ordinal regression model. ResultsIn the 226 patients that were included, the median lesion growth was 22 (IQR 10-45) ml. In the multivariable model, lower collateral capacity [aOR: 0.62 (95% CI: 0.44-0.87); p = 0.01], longer time to treatment [aOR: 1.04 (1-1.08); p = 0.04], unsuccessful recanalization [aOR: 0.57 (95% CI: 0.34-0.97); p = 0.04], and larger midline shift [aOR: 1.18 (95% CI: 1.02-1.36); p = 0.02] were associated with late lesion growth. ConclusionLate, subacute, lesion growth occurring between 1 day and 1 week after ischemic stroke treatment is influenced by lower collateral capacity, longer time to treatment, unsuccessful recanalization, and larger midline shift. Notably, these risk factors are similar to the risk factors of acute lesion growth, suggesting that understanding and minimizing the effects of the predictors for late lesion growth could be beneficial to mitigate the effects of ischemia